This phase I/II trial studies the side effects and the best dose of veliparib when given together with bendamustine hydrochloride and rituximab and to see how well they work in treating patients with lymphoma, multiple myeloma, or solid tumors that have come back or have not responded to treatment. Veliparib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Giving veliparib together with bendamustine hydrochloride and rituximab may kill more cancer cells.

MTD of veliparib and bendamustine hydrochloride combination based on the incidence of dose-limiting toxicity graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCATE) version 4.0 (Phase Ib) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Response rate (best response at any point on therapy) in patients with non-Hodgkin lymphoma treated with veliparib, bendamustine hydrochloride and rituximab using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Phase IIa) [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: No ]

Duration of remission (Phase IIa) [ Time Frame: From the first documented response to the first documented progression or death, assessed up to 30 days post-treatment ] [ Designated as safety issue: No ]

Overall survival (Phase IIa) [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: No ]

Kaplan-Meier estimates will be calculated and log-rank tests will be employed when certain comparisons are needed.

Progression-free survival using RECIST version 1.1 (Phase IIa) [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 30 days post-treatment ] [ Designated as safety issue: No ]

Kaplan-Meier estimates will be calculated and log-rank tests will be employed when certain comparisons are needed.

Patients receive veliparib PO BID on days 1-7 and bendamustine hydrochloride IV over 30-60 minutes on days 1-2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Once the maximum-tolerated dose is determined, a cohort of patients receives veliparib and bendamustine hydrochloride as above and rituximab IV on day 1. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: Bendamustine Hydrochloride

Given IV

Other Names:

Bendamustin Hydrochloride

BENDAMUSTINE HYDROCHLORIDE

Cytostasan Hydrochloride

Ribomustin

SyB L-0501

Treanda

Other: Pharmacological Study

Correlative studies

Biological: Rituximab

Given IV

Other Names:

BI 695500

C2B8 Monoclonal Antibody

Chimeric Anti-CD20 Antibody

IDEC-102

IDEC-C2B8

IDEC-C2B8 Monoclonal Antibody

MabThera

Monoclonal Antibody IDEC-C2B8

PF-05280586

Rituxan

RITUXIMAB

Rituximab Biosimilar BI 695500

Rituximab Biosimilar PF-05280586

Rituximab Biosimilar RTXM83

RTXM83

Drug: Veliparib

Given PO

Other Names:

ABT-888

PARP-1 inhibitor ABT-888

VELIPARIB

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated dose (MTD) of ABT-888 (veliparib) in combination with bendamustine (bendamustine hydrochloride) in patients with solid tumors, lymphoma, or multiple myeloma. (Phase Ib) II. To establish the safety of ABT-888 in combination with bendamustine and rituximab in an expansion cohort of patients with non-Hodgkin lymphoma (NHL). (Phase Ib) III. To assess the toxicity profile of this regimen in the above patients. (Phase Ib) IV. To determine the complete response (CR) rate in patients with indolent NHL or mantle cell lymphoma (MCL) treated with ABT-888 + bendamustine + rituximab. (Phase IIa)

OUTLINE: This is a phase I, dose-escalation study of veliparib followed by a phase II study.

Patients receive veliparib orally (PO) twice daily (BID) on days 1-7 and bendamustine hydrochloride intravenously (IV) over 30-60 minutes on days 1-2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Once the maximum-tolerated dose is determined, a cohort of patients receives veliparib and bendamustine hydrochloride as above and rituximab IV on day 1. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Phase 1b: Patients must have a histologically confirmed solid malignancy, lymphoma or multiple myeloma for which standard curative or palliative measures do not exist, are no longer effective, or for which the patient is not eligible or refuses; phase 1b cohort expansion: patients must have a histologically confirmed cluster of differentiation (CD)-20 positive B-cell non-Hodgkin lymphoma for which standard curative or palliative measures do not exist, are no longer effective, or for which the patient is not eligible or refuses; phase 2a: patients must have histologically or cytologically confirmed marginal zone B-cell lymphoma, small lymphocytic lymphoma, lymphoplasmacytic lymphoma or mantle cell lymphoma, and must have at least one measureable site of disease

For lymphoma and multiple myeloma patients: patients who have relapsed or are refractory to at least one prior chemotherapeutic regimen or biologic agent; patients must either be ineligible for or have refused curative options for treatment, including stem cell transplant, if applicable

For solid tumor patients: relapsed or refractory to at least one prior chemotherapeutic regimen or biologic agent; patients must either be ineligible for or have refused curative options for treatment

Patients must have had a rest period of at least 3 weeks since prior chemotherapy or radiation therapy, 6 weeks if the last regimen included carmustine (BCNU) or mitomycin C; there must be a rest period of at least 3 months if the last therapy was immunotherapy or radioimmunotherapy (unless the disease has progressed since treatment)

Patients with prior stem cell transplant will be eligible as long as they have not relapsed or progressed within 100 days post-transplant and they meet the above inclusion criteria

Women of child-bearing potential and men must agree to use adequate contraception (hormonal, barrier method of birth control, or abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Ability to understand and the willingness to sign a written informed consent document

Toxicities from prior therapies must have resolved to baseline, or be =< grade 2 and stable for at least one month

Patient must be able to swallow pills

Patients with central nervous system (CNS) metastases must be stable after therapy for > 3 months and off steroid treatment prior to study enrollment

Exclusion Criteria:

Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered to baseline (or are not at stable grade =< 2) from adverse events due to agents administered more than 3 weeks earlier; patients who have received immunotherapy or radioimmunotherapy within 3 months, unless disease has progressed since treatment; patients who have been administered ABT-888 as part of a single or limited dosing study, such as a phase 0 study, will not be excluded from participating in this study solely because of receiving prior ABT-888

Patients may not be receiving any other investigational agents

History of allergic reactions attributed to compounds of similar chemical or biologic composition to ABT-888, bendamustine or mannitol; patients enrolling in the cohort expansion or phase 2 portions of the study who have been intolerant of repeated doses of rituximab in the past will be excluded (patients who have had infusion reactions to their initial dose of rituximab will not be excluded)

Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ABT-888

Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are eligible if their HIV is under adequate control with an antiretroviral regimen that has been stable for >= 4 weeks, as long as the CD4 count is > 300; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated; patients on zidovudine or stavudine would not be eligible

Patients with active seizure or a history of seizure are not eligible

Patients with uncontrolled CNS metastasis are not eligible

Patients with unrelated prior malignancies must have undergone potentially curative therapy for their prior malignancy, have no evidence of that disease for three years, or be deemed at low risk for recurrence of their prior malignancy by her/his treating physician; patients with dermal squamous cell carcinoma, basal cell carcinoma or melanoma in situ that has been completely excised will be eligible following excision

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01326702